Alcohol use disorders (alcohol abuse and alcohol dependency) are among the most prevalent mental disorders worldwide and and are associated with substantial personal and societal costs Both acute and chronic consumption of alcohol have been shown to place individuals at risk for health problems including alcohol dependence, increased risks for neural disorders, cardiovascular disease, cancers, and liver injury. Lohocla Research Corporation has developed, through rational design, a novel, patent-protected new chemical entity assigned the acronym DCUKA. DCUKA simultaneously targets two neurochemical processes influencing alcohol intake. Our preclinical studies demonstrate that DCUKA reduces alcohol withdrawal hyperexcitability, is neuroprotective, reduces anxiety, reduces relapse drinking and lessens overall alcohol intake. Lohocla intends to position DCUKA not just for the treatment of alcohol dependence (as current treatments do), but also for individuals who are drinking alcohol at hazardous/harmful levels and wish to reduce them to safer levels. In order for Lohocla to begin testing DCUKA in humans, specific FDA-required pharmacokinetic and toxicological preclinical investigations must be completed. The following studies will be accomplished during funding of this application: (1) Further establish the effectiveness of DCUKA in reducing alcohol intake in non-dependent animals; (2) Develop a sensitive assay based on mass spectrometry detection for assaying DCUKA in blood and tissues; (3) ascertain in vivo oral pharmacokinetics and in vitro metabolism of DCUKA in liver microsomes; and (4) toxicology and safety studies in rats (acute and multiple dose tolerance, genetic toxicity, chronic toxicity, acute CNS safety). Completion of these studies will allow Lohocla research to file for an exploratory IND and, thereby, position DCUKA for an IND application. [unreadable] [unreadable] [unreadable]